文献类型：期刊文献

英文题名：Metabolomics Analysis Revealed ThatSXZAmeliorates Cognitive Impairment in Naturally Aged Rats by Promoting Glutathione Metabolism and Inhibiting the Ferroptosis Pathway

作者：Liu, Mengya[1];Li, Shunyi[2];Liang, Yonglin[2];Zhang, Yugui[2];Jia, Xutong[1];Duan, Yongqiang[1];Bai, Min[1]

第一作者：Liu, Mengya

通信作者：Duan, YQ[1];Bai, M[1]

机构：[1]Ningxia Med Univ, Yinchuan, Ningxia, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China

第一机构：Ningxia Med Univ, Yinchuan, Ningxia, Peoples R China

通信机构：[1]corresponding author), Ningxia Med Univ, Yinchuan, Ningxia, Peoples R China.

年份：2026

卷号：32

期号：10

外文期刊名：CNS NEUROSCIENCE & THERAPEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001895750300001)】；

基金：The financial support from Science and Technology Plan of Gansu Province [24JRRA565, 2023-ZD-236, zyzx-2024-zx15] facilitated the acquisition of essential resources, access to research facilities, and the execution of this study.

语种：英文

外文关键词：age-related cognitive impairment; ferroptosis; glutathione metabolism; metabolomics; Shenxian Zhou

摘要：Objective This study aimed to examine the potential neuroprotective effects of SXZ on cognitive impairment in naturally aging rats and to explore the underlying molecular mechanisms.Methods Eighteen-month-old Sprague-Dawley rats were used as a natural aging model and administered Shenxian Zhou (SXZ) for 6 months. Cognitive function was assessed using behavioral evaluations. Hematoxylin-eosin, Nissl, and immunofluorescence staining for NeuN were performed to evaluate neuronal pathology in aging rats. Metabolomics analysis was performed to characterize hippocampal metabolites, followed by molecular validation.Results SXZ attenuated age-related cognitive decline and reduced hippocampal pathological and neuronal damage in naturally aging rats. SXZ-H significantly modulated glutathione metabolism and ferroptosis-associated signaling pathways. Transmission electron microscopy revealed mitochondrial morphological changes consistent with ferroptosis in hippocampal neurons of naturally aging rats. Molecular biology experiments further indicated that, subsequent to SXZ-H intervention, lipid peroxidation and oxidative stress levels were significantly reduced. Furthermore, expression levels of p53 and Keap1 genes and proteins were significantly downregulated, whereas the expression of SLC7A11, GPX4, Nrf2, and HO-1 genes and proteins was notably upregulated.Conclusion SXZ-H effectively mitigates cognitive impairment in naturally aging rats, an effect that may be mediated by promoting glutathione metabolism and regulating key ferroptosis-related proteins, thereby inhibiting neuronal ferroptosis.